Anti-HIV-1 activity of indolicidin, an antimicrobial peptide from neutrophils.
Indolicidin is a tridecapeptide amide isolated from the cytoplasmic granules of bovine neutrophils. It has potent, broad spectrum microbicidal activities in vitro that are thought to be related to the membrane-disruptive properties of the peptide. Based on the putative membrane-targeted mode of action, we postulated that indolicidin would be active against HIV-1, an enveloped virus. Indolicidin was reproducibly virucidal against HIV-1 at a concentration of 333 microg/mL (174 microM) with a 50% inhibitory dose between 67 and 100 microg/mL. At 37 degrees C, killing was rapid with >50% killing of HIV occurring within 5 min, and nearly 100% viral inactivation achieved by 60 min. The anti-HIV activity of indolicidin was temperature-sensitive, a finding consistent with a membrane-mediated antiviral mechanism. Parallel experiments revealed that indolicidin lysed cultured lymphoblastoid cells at concentrations similar to those required for antiviral activity. However, a des-R13-amide indolicidin analog (R12-OH), previously shown to have less antibacterial activity than indolicidin, was significantly less active against HIV and was non-toxic to lymphoid target cells at concentrations up to 333 microg/mL, the highest level tested.
Robinson
W E
WE
Department of Pathology, University of California, Irvine 92697-4800, USA. ewrobins@uci.edu
McDougall
B
B
Tran
D
D
Selsted
M E
ME
D000818:Animals; D019380:Anti-HIV Agents / Q000138:chemical synthesis / Q000494:pharmacology* / Q000633:toxicity; D023181:Antimicrobial Cationic Peptides; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects; D002417:Cattle; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D009504:Neutrophils / Q000502:physiology*; D010455:Peptides / Q000138:chemical synthesis / Q000494:pharmacology* / Q000633:toxicity; D013329:Structure-Activity Relationship; D013696:Temperature
D019380:Anti-HIV Agents; D023181:Antimicrobial Cationic Peptides; D010455:Peptides; C073143:indolicidin